Trihalobenzene compounds

ABSTRACT

Compounds of the formula: ##STR1## wherein X is selected from bromine and chlorine useful as intermediates in the preparation of insecticidal compounds.

This is a division of application Ser. No. 052,969, filed May 22, 1987,now U.S. Pat. No. 4,788,349.

This invention relates to novel halogenated diphenyl ethers, useful asintermediates in the preparation of insecticidal compounds, and tomethods and intermediates for their preparation.

In a first aspect, the invention provides novel compounds of formula(I): ##STR2## wherein X is selected from bromine and chlorine. Thespecific compounds according to the invention are:

4-bromo-1-fluoro-2-phenoxybenzene, and

4-chloro-1-fluoro-2-phenoxybenzene

The compounds of formula (I) are particularly useful as intermediatesfor the preparation of insecticides. UK Patent Specification No.1,561,575 discloses the use of 1-bromo-3-phenozybenzene as anintermediate in the preparation of insecticidally activealpha-trifluoromethyl-3-phenoxy-benzyl esters of carboxylic acids. Useof the compound of formula (I) wherein X is bromine in a manneranalogous to that described in UK Patent Specification No. 1,561,575provides alpha-trifluoromethyl-3-phenoxy-4-fluorobenzyl alcohol. Thisprocess is illustrated in Scheme I. ##STR3##

The compound of formula (I) wherein X is bromine may also be used in thepreparation of 4-fluoro-3-phenoxybenzaldehyde, a useful intermediate inthe preparation of insecticidal compounds, for example4-fluoro-3-phenoxybenzyl esters of cyclopropanecarboxylic acids andalpha-substituted derivatives thereof. One method of preparing4-fluoro-3-phenoxybenzaldehyde follows the method of Olah and Arvanaghi,Angewandte Chemie, International Edition, 20, p 878, 1981 and isillustrated in Scheme II. ##STR4##

4-Fluoro-3-phenoxybenzaldehyde may also be prepared from4-bromo-1-fluoro-2-phenoxybenzene by the method of Einhorn and Luche,Tetrahedron Letters, 27, p 1791, 1986, as illustrated in Scheme III:##STR5##

4-Fluoro-3-phenoxybenzaldehyde is a useful intermediate in thepreparation of 4-fluoro-3-phenoxybenzyl alcohol and itsalpha-substituted derivatives, and insecticidal esters thereof. Anexample of its use is in the preparation ofalpha-cyano-4-fluoro-3-phenoxybenzyl3-(2-chloro-3,3,3-trifluoroprop-1-en-1-yl)-2,2-dimethylcyclopropanecarboxylate,according to the method described in UK Patent Application No.2,161,804A. This process is illustrated in Scheme IV. ##STR6##

A further use of the compounds of formula (I) is in the preparation ofcompounds of formula (II), wherein R represents alkyl, useful asintermediates in the preparation of the insecticidal compounds describedin the applicants' copending UK Patent Application No. 8703741. ##STR7##

The compounds of formula (II) may be prepared from the compounds offormula (I) by the Heck reaction, using, for example, the method ofJeffery, Chemical Communications, 1984, p 1287. The preparation ofmethyl 3-(4-fluoro-3-phenoxyphenyl)propenoate from4-bromo-1-fluoro-2-phenoxybenzene, and the subsequent conversion to1,1,1-trifluoro-2-(4-ethoxyphenyl)-5-(4-fluoro-3-phenoxyphenyl)pentane,a compound which is disclosed in UK Patent Application No. 8703741, isillustrated in Scheme V.

In a further aspect, the invention provides a first process forpreparing the compounds of formula (I), which comprises as a first stepthe diazotisation of 2-fluoro-5-haloanilines of formula (III): ##STR8##wherein X is selected from bromine and chlorine, followed by theaddition of the resultant diazonium salt solution to a cooled solutionof an alkali metal iodide, for example, potassium iodide. This processleads to the formation of 4-halo-1-fluoro-2-iodobenzenes of formula(IV): ##STR9## The compounds of formula (IV) may then be converted tothe compounds of formula (I) by reaction with phenol in the presence ofa strong base and an Ullmann catalyst, such as copper or a copper salt,for example cuprous chloride. This process is illustrated, by way ofexample in Scheme VI. ##STR10##

The 4-halo-1-fluoro-2-iodobenzenes of formula (IV) are believed to benovel. In a further aspect, therefore, the invention provides compundsof formula (IV), wherein X is selected from bromine and chlorine.

The compounds of formula (I) wherein X is bromine may also be preparedfrom 4-fluoro-3-phenoxybenzaldehyde. In a further aspect therefore, theinvention provides a second process for the preparation of the compoundsof formula (I), in which 4-fluoro-3-phenoxybenzaldehyde is firstoxidised to 4-fluoro-3-phenoxybenzoic acid, for example by the action ofsodium periodate in the presence of ruthenium trichloride, using themethod of Carlsen and Sharpless, Journal of Organic Chemistry, 46, 3936,1981. The acid is then converted to the acid chloride derivative using,for example, thionyl chloride. 4-Bromo-1-fluoro-2-phenoxybenzene maythen be obtained from the acid chloride by reaction withbromotrichloromethane in the presence of an alkali metal salt of2-pyridinethiol 1-oxide and a radical initiator using the methodillustrated by Barton et al, Tetrahedron Letters, 24, 4979, 1983;Tetrahedron Letters, 26, 5939, 1985. This process is illustrated inScheme VII. ##STR11##

Further details of the processes of the invention are given in thefollowing Examples.

In the Examples the products were usually identified and characterisedby means of Nuclear Magnetic Resonance spectroscopy and infra redspectroscopy. In each case where a product is specifically named itsspectral characteristics are consistent with the assigned structure.Except where stated otherwise, exemplified compounds having one or moreasymmetrically substituted carbon atoms were prepared in racemic form.

In the Examples, Gas Liquid Chromatography (GLC) retention times weredetermined on a Hewlett Packard 5890 Gas Chromatograph, using aChromopak C.P. Sil 5 C.B. column of 12.5M length and 0.2 mm internaldiameter. Unless otherwise stated, the injection temperature was 100°C., and a temperature gradient of 15° C./minute employed, up to amaximum temperature of 280° C., maintained for 4 minutes. The carriergas was helium at a column head pressure maintained at 11 psi.Alternative injection and maximum temperatures are indicated in theExamples where appropriate.

¹ H Nuclear Magnetic Resonance (NMR) spectrometry was performed at afrequency of 270 MHz on a Jeol FX 270 NMR spectrometer, unless otherwiseindicated. 90 MHz, 60 MHz and 400 MHz ¹ H NMR spectrometry wereperformed using Jeol FX 90Q, Jeol PMX 60SI and Jeol GX400 spectrometersrespectively.

¹⁹ F NMR spectrometry was performed on a Jeol FX90Q spectrometer at afrequency of 84.26 MHz. All NMR shift values are quoted in ppm relativeto a standard (TMS or CFCl₃).

Molecular Ion (M⁺) peaks were determined on one of three massspectrometers: Jeol DX303, Kratos MS80 or Hewlett Packard HP 5992.

EXAMPLE 1

This Example illustrates the preparation of4-bromo-1-fluoro-2-iodobenzene.

A solution of sodium nitrite (1.71 g) in water (4 cm³) was addeddropwise to a stirred mixture of 5-bromo-2-fluoroaniline (4.5 g), water(15 cm³), ice (15 g) and concentrated sulphuric acid (1.8 cm³) at atemperature maintained at 0°-5° C. The reaction mixture was stirred for30 minutes, and further concentrated sulphuric acid (0.4 cm³) added. Theresultant solution, containing 5-bromo-2-fluorobenzenediazoniumsulphate, was then added dropwise to a solution of potassium iodide(4.23 g) in water (10 cm³) at a temperatue of 5°-6° C.; vigorouseffervescence was observed during the addition. When the addition wascomplete, the reaction mixture was allowed to warm to the ambienttemperature (22° C.) and was then extracted twice with diethyl ether.The combined extracts were washed successively with brine and sodiumthiosulphate solutions, dried over anhydrous magnesium sulphate,filtered and concentrated by evaporation of the solvent under reducedpressure. The residual oil was purified by flash column chromatography,using a silica gel support and eluting with petroleum ether (boilingrange 40°-60° C.) containing 4% by volume diethyl ether, to give4-bromo-1-fluoro-2-iodobenzene (4.63 g) as a colourless oil.

¹ H nmr (CDCl₃): 6.95 (dd, 1H); 7.40 (m, 1H); 7.90 (dd, 1H).

Infra red (liquid film): 3090, 1580, 1470, 1370, 1260, 1240, 1230, 1130,1082, 1070, 1040, 875, 820, 670, 620 cm⁻¹.

EXAMPLE 2

This Example illustrates the preparation of4-bromo-1-fluoro-2-phenoxybenzene.

A solution of phenol (0.515 g) in N,N-dimethylformamide (10 cm³) wasadded dropwise to a suspension of sodium hydride (0.329 g) inN,N-dimethylformamide (10 cm³) at a temperature of 0° C. under an inertatmosphere of nitrogen. When the addition was complete, the coolingsource was removed and the mixture stirred for 2 hours at the ambienttemperature (22° C.). Cuprous chloride (0.452 g) and a solution of4-bromo-1-fluoro-2-iodobenzene (1.37 g) in N,N-dimethylformamide (10cm³) were added to the mixture, which was heated at 100° C. for 17hours; at this time, the reaction mixture was shown by gas liquidchromatography to contain only a small residue of the unreacted startingmaterial. The mixture was cooled and extracted with diethyl ether. Theextract was washed twice with water and once with brine, dried overanhydrous magnesium sulphate, filtered and concentrated by evaporationof the solvent under reduced pressure. The residual oil was passedthrough a short column of silica gel, using petroleum ether (boilingrange 40°-60° C.) containing 10% by volume diethyl ether as eluent.Evaporation of the solent under reduced pressure gave a clear, palebrown oil (0.92 g). Distillation of this oil at reduced pressure (0.03mmHg) yielded a number of fractions in a boiling range of 50°-80° C. Twoof these fractions were shown by thin layer chromatography to containprincipally a single reaction product. These two fractions were combinedand purified by preparative thin layer chromatography on a silica gelsupport, using petroleum ether (boiling range 40°-60° C.) as eluent.4-Bromo-1-fluoro-2-phenoxybenzene (0.052 g) was obtained as a colourlessoil by evaporation of the eluent under reduced pressure.

¹ H nmr (CDCl₃): 6.9-7.4 (m)

270 MHz ¹³ C nmr (CDCl₃): B 156.46 (s, 1C); 153.33 (d, 1C); 145.10 (d,1C); 129.91 (s, 2C); 127.21 (d, 1C); 124.20 (s, 1C); 123.94 (s, 1C);118.31 (d, 1C); 117.97 (s, 2C); 116.34 (d, 1C).

Infra red (liquid film): 3100-3000, 3000-2800, 1600, 1495, 1450, 1405,1275, 1250, 1220, 1190, 1170, 1120, 1075, 1025, 910, 880, 810, 755, 695,630 cm⁻¹.

EXAMPLE 3

This Example illustrates the preparation of 4-fluoro-3-phenoxybenzoicacid.

4-Fluoro-3-phenoxybenzaldehyde (15 g) was dissolved in a mixture ofcarbon tetrachloride (138 cm³) and acetonitrile (138 cm³), and water(207 cm³) was added. Sodium periodate (31.21 g) was added and themixture stirred vigorously whilst hydrated ruthenium chloride (0.35 g)was added. After two hours of stirring at the ambient temperature,analysis by thin layer chromatography showed some remaining aldehyde.Further sodium periodate (31.21 g) was added and stirring continued for1 hour, at which time analysis by thin layer chromatography showed nostarting material. The mixture was partitioned between dichloromethaneand water, and the aqueous phase separated and extracted three furthertimes with dichloromethane. The combined organic layers were dried overanhyrous magnesium sulphate and the solvents evaporated under reducedpressure to give a brown oil, which was dissolved in diethyl ether andshaken with aqueous sodium hydroxide solution to extract the acid as thesodium salt. Acidification of the aqueous solution gave a white solidwhich was re-extracted with diethyl ether. The ethereal layers werewashed with water, dried over anhydrous magnesium sulphate and thesolvent evaporated under reduced pressure to give the title compound asa white solid (13.35 g).

¹ H NMR (CDCl₃) (ppm): 6.8-7.4 (6H, m); 7.6-7.9 (2H, m); 11.9 (1H,broad)

EXAMPLE 4

This Example illustrates the preparation of 4-fluoro-3-phenoxybenzoylchloride.

4-Fluoro-3-phenoxybenzoic acid (13.35 g) was mixed with thionyl chloride(65 cm³) and the mixture heated at the reflux temperature for 20minutes. The mixture was cooled and excess thionyl chloride evaporatedunder reduced pressure to leave the acid chloride as a brown oil (14.87g). This product was used directly in the method of the followingExample.

EXAMPLE 5

This Example illustrates the preparation of4-bromo-1-fluoro-2-phenoxybenzene.

The sodium salt of 2-pyridinethiol 1-oxide (8.85 g) was suspended inbromotrichloromethane (297 cm³) under an atmosphere of nitrogen in areaction vessel covered with aluminium foil to exclude light. Thestirred mixture was heated to the reflux temperature and a solution of4-fluoro-3-phenoxybenzoyl chloride (14.87 g) and ,-azo-bis-isobutyronitrile (1.67 g) in bromotrichloromethane (297 cm³)was added dropwise to the refluxing mixture over 90 minutes using asyringe pump. Refluxing was continued for a further 1 hour, at whichtime analysis of a withdrawn sample by gas liquid chromatography showedonly a trace of remaining acid chloride.

The mixture was cooled and partitioned between water anddichloromethane. The aqueous layer was separated and extrated twice withdichloromehane. The combined organic layers were washed with brine,dried over anhydrous magnesium sulphate and concentrated by evaporationunder reduced pressure to leave a brown oil. Traces of acid and acidchloride were removed by stirring the product in two molar aqueoussodium hydroxide solution for 10 minutes. Acidification of the aqueoussolution gave 7.05 g of recovered 4-fluoro-3-phenoxybenzoic acid. Thereaction product was extracted from the aqueous solution with diethylether, the ether layer dried over anhydrous magnesium sulphate and thesolvent evaporated under reduced pressure to give a brown oil. This oilwas purified by column chromatography on silica gel, eluting withpetroleum ether (boiling range 60°-80° C.) containing 10% by volumediethyl ether. Two products were obtained in separately elutedfractions:

Product A

¹ H NMR (CDCl₃) (ppm): 8.75 (1H, m); 7.80 (2H, m); 7.40 (1H, m)

GLC retention time: 3.36 minutes

Identified by mass and NMR spectrometry as2-(trichloromethylthio)pyridine

Product B: (5.65 g)

¹ H NMR (CDCl₃) (ppm): 6.95-7.4 (aromatic H, m)

Infra red (liquid film): 1589, 1488, 1269, 1213 cm⁻¹ (major peaks only)

Molecular ion: 266/268

GLC retention time: 4.42 minutes

Identified as the required 4-bromo-1-fluoro-2-phenoxybenzene.

I claim:
 1. A compound of formula: ##STR12## wherein X is selected frombromine and chlorine.
 2. 4-Bromo-1-fluoro-2-iodobenzene. 3.4-Chloro-1-fluoro-2-iodobenzene.